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ID PMID Title PublicationDate abstract
28674691 Influence of Cigarette Smoking on Rheumatoid Arthritis Risk in the Han Chinese Population. 2017 OBJECTIVES: Cigarette smoking has been shown in European populations to be associated with rheumatoid arthritis (RA) susceptibility. This study aims to examine the association of smoking with RA in the Han Chinese population. METHODS: 718 Han Chinese RA patients and 404 healthy controls were studied. The associations of cigarette smoking (current, former or ever vs. never smokers, and pack-years of exposure) with RA, anti-cyclic citrullinated peptide antibody (ACPA) positive RA, IgM rheumatoid factor (RF) positive RA, and baseline radiographic erosions (modified van der Heijde-Sharp scores) were assessed. The interaction between smoking and the HLA-DRB1 shared epitope (SE) in RA was also examined. RESULTS: In this study, 11 (1.53%) cases and 6 (1.49%) controls were former smokers (p = 0.95), while 95 (13.23%) cases and 48 (11.88%) controls were current smokers (p = 0.52). Trends toward associations between smoking status (ever vs. never) with RA-overall (p = 0.15, OR = 1.44), ACPA-positive RA (p = 0.24, OR = 1.37), RF-positive RA (p = 0.14, OR = 1.46), or the presence of radiographic erosions (p = 0.66, OR = 1.28) were observed although individually here were not statistically significant. There was no evidence of statistical interaction between smoking status (ever vs. never) and SE for all RA, ACPA-positive RA, ACPA-negative RA, RF-positive RA, RF-negative RA (p = 0.37, 0.50, 0.24, 0.26, and 0.81 respectively), and the 95% CI for the attributable proportion for all interactions included 0. CONCLUSION: This is the first study to examine the association of cigarette smoking with RA in the Han Chinese population. This study shows a trend toward an interaction between smoking and SE carriage influencing the risk of RA, though findings were not statistically significant. It is possible that in the presence of universal exposure to heavy air pollution the effect of smoking on RA risk may be obscured.
29113115 Ferulaldehyde Improves the Effect of Methotrexate in Experimental Arthritis. 2017 Nov 6 Methotrexate (MTX) is still the gold standard for treatment of rheumatoid arthritis (RA). The therapeutic efficacy of low-dose of MTX can be increased by its combination with a natural substance, ferulaldehyde (FRA). The aim of this study was to evaluate the effect FRA and MTX administered alone or in combination in adjuvant arthritis. The disease was induced to Lewis male rats by intradermal injection, which contains a suspension of heat-inactivated Mycobacterium butyricum in incomplete Freund's adjuvant. The experiment of 28 days included: healthy animals, arthritic animals, arthritic animals with administration of FRA at the oral daily dose of 15 mg/kg, arthritic animals with administration of MTX at the oral dose of 0.3 mg/kg twice a week, and arthritic animals administered with FRA and MTX. FRA in monotherapy decreased significantly only the level of interleukin-1β (IL-1β) and matrix metalloproteinase-9 in plasma. Combination of FRA and low-dose MTX was more effective than MTX alone when comparing body weight, hind paw volume, arthritic score, plasmatic levels of IL-1β, activity of γ-glutamyl transferase, and relative mRNA expression of IL-1β in the spleen. Therefore, the combination treatment was the most effective. The obtained results are interesting for future possible innovative therapy of patients with RA.
28901166 The in vitro and in vivo anti-inflammatory activities of alphitonin-4-O-β-D-glucopyranosi 2018 Nov The anti-inflammatory compound, alphitonin-4-O-β-D-glucopyranoside (1), has previously been isolated in the leaves of Artokapus tonkinensis and synthesised from taxifolin. This study aimed to investigate the inhibitory effect of this compound on inflammatory cytokines, including tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1, IL-6 and IL-10, in RAW264.7 macrophages and in an arthritis animal model. Compound 1 dose-dependently decreased the production of TNF-α, IL-1 and IL-6 in lipopolysaccharide-stimulated RAW264.7 cells. In contrast, the level of anti-inflammatory IL-10 increased. In a collagen antibody-induced arthritis BALB/c mouse model, compound 1 at a dose of 125 and 250 mg/kg body weight significantly decreased arthritis incidence in comparison with dexamethasone.
28906466 Therapeutic Effect of Exogenous Truncated IK Protein in Inflammatory Arthritis. 2017 Sep 14 Inhibitor K562 (IK) protein was first isolated from the culture medium of K562, a leukemia cell line. It is known to be an inhibitory regulator of interferon-γ-induced major histocompatibility complex class (MHC) II expression. Previously, we found that transgenic (Tg) mice constitutively expressing truncated IK (tIK) showed reduced numbers of pathogenic Th1 and Th17 cells, which are known to be involved in the development of rheumatoid arthritis (RA). Here, we investigated whether exogenous tIK protein has a therapeutic effect in arthritis in disease models and analyzed its mechanism. Exogenous tIK protein was produced in an insect expression system and applied to the collagen antibody-induced arthritis (CAIA) mouse disease model. Injection of tIK protein alleviated the symptoms of arthritis in the CAIA model and reduced Th1 and Th17 cell populations. In addition, treatment of cultured T cells with tIK protein induced expression of A20, a negative regulator of nuclear factor-κB (NFκB)-induced inflammation, and reduced expression of several transcription factors related to T cell activation. We conclude that exogenous tIK protein has the potential to act as a new therapeutic agent for RA patients, because it has a different mode of action to biopharmaceutical agents, such as tumor necrosis factor antagonists, that are currently used to treat RA.
27318181 IgG4-related sialadenitis and Sjögren's syndrome. 2017 Mar IgG4-related disease (IgG4-RD) has emerged as a new entity in the last decade. It comprises numerous conditions previously thought to be unrelated. Macroscopically, these diseases cause diffuse organ swelling and formation of pseudotumorous masses. Histopathologically, they are characterized by a lymphoplasmacytic infiltrate with increased IgG4+ plasma cells and storiform fibrosis. Despite rapid progress within the last years, our knowledge on these conditions is still fragmented. To date, more than forty organs have been reported to be included in IgG4-RD, and salivary gland involvement is amongst the most common organs affected [IgG4-related sialadenitis (IgG4-RS)]. Interestingly, IgG4-RS shares commonalities with Sjögren's syndrome (SS), like glandular enlargement, sicca symptoms, arthralgias, hypergammaglobulinemia, hypocomplementemia, and circulating antinuclear antibodies. Nonetheless, they differ in that the incidence of anti-Ro and anti-La reactivity is not frequently found in patients with IgG4-RS, their salivary glands are infiltrated by a large number of IgG4+ plasma cells and IgG4-RS symptoms respond promptly to steroids. The aim of this review was to describe the clinical, serological, histopathological and pathophysiological aspects of IgG4-RS in the context of IgG4-RD and highlight the differences between IgG4-RS and SS.
28735431 A systematic review of primary Sjögren's syndrome in male and paediatric populations. 2017 Oct Primary Sjögren's syndrome (pSS) is a chronic multisystem autoimmune rheumatic disease characterised by female predominance. Although the disease is rare in the male and paediatric populations, it has been suggested that it may have a different disease phenotype, which has not been investigated before using a systematic approach. A systematic literature search of PubMed databases (updated to December 2016) was performed to identify all published data on the epidemiological, clinical and laboratory manifestations of pSS in the male and paediatric populations. The literature search of the male and paediatric pSS studies identified 2025 and 186 citations, respectively, out of which 7 and 5 fulfilled our inclusion criteria and were analysed further. The range of age at disease onset was 9.4-10.7 years for children and 39.4-56.9 years at diagnosis for male patients. We identified a prevalence of extra-glandular manifestations between 52.6-92.3% in the male population and 50.0-84.6% in children, while abnormal sialometry was only reported in the paediatric population, with a prevalence between 71.4 and 81.8%. There was a significant variation of positive serological markers, with anti-Ro antibodies reported between 15.7-75.0% and 36.4-84.6%, and anti-La antibodies between 5.6-51.7% and 27.3-65.4%, in the male and paediatric populations, respectively. The characteristics of pSS in the male and paediatric populations varied according to different studies. When compared to data available from pSS adult populations, children diagnosed with pSS reported less dryness and had a higher prevalence of parotitis, lymphadenopathy and systemic symptoms and male patients were younger at the time of diagnosis. This systematic review contributes to a better understanding of the epidemiology of pSS in rare populations. Large longitudinal cohort studies comparing male with female patients and adult with paediatric patients are needed.
28507729 Difference in clinical presentation between women and men in incident primary Sjögren's s 2017 BACKGROUND: A more severe disease phenotype has been reported in men compared to women in several rheumatic diseases. However, studies have not conclusively established sex-related clinical features in primary Sjögren's syndrome (pSS). In this study, we therefore investigated the clinical presentation of pSS in women and men at diagnosis. METHODS: Incident, treatment naïve patients (n = 199) during a 5-year period in a specified area were prospectively included and examined for items of classification criteria for pSS as well as extraglandular manifestations (EGM). Serum was sampled at the time of diagnosis and anti-Ro52/SSA levels were measured by ELISA. Replication of significant findings was confirmed in an independent cohort of pSS patients (n = 377), and meta-analysis was performed. RESULTS: An increased frequency of extraglandular manifestations in men was observed and replicated (p = 0.05, p = 0.0003, and p(meta) = 0.002). This related to pulmonary involvement, vasculitis, and lymphadenopathy being more common in men, for whom a lower age at diagnosis was observed in the exploratory cohort. Additionally, SSA-positive male patients had significantly higher levels of anti-Ro52 levels than their female counterparts in sera available for analysis (p = 0.02). CONCLUSIONS: Our analysis of two independent cohorts of incident pSS demonstrates that the presence and number of EGM are significantly more frequent among men with pSS than women at diagnosis. Importantly, around half of the male patients presented with more than one EGM at diagnosis, supporting the conclusion that pSS in men represents a more severe form of disease, regardless of the lower risk for men to develop pSS.
29018566 Risks of smoking and benefits of smoking cessation on hospitalisations for cardiovascular 2017 OBJECTIVES: To investigate the associations between smoking status, smoking cessation and hospitalisations for cardiovascular events (CVE) and respiratory tract infections (RTI) in an inception cohort of patients with rheumatoid arthritis (RA). METHODS: The study was set within UK primary care electronic health records (the Clinical Practice Research Datalink) linked to hospital inpatient data (Hospital Episode Statistics). Patients with RA were followed from diagnosis to hospitalisation with a record of CVE or RTI, leaving their general practice, death, or 10 January 2012, whichever was earliest. Smoking status (never, current, former) was defined using primary care data and could vary over time. Survival analysis was performed using Cox regression (first event) and conditional risk set models (multiple RTIs). RESULTS: 5677 patients were included in the cohort: 68% female, median age 61 years. The age-adjusted and sex-adjusted risks of hospitalisation for CVE or RTI were more than twice as high in current vs never smokers (CVE HR (95% CI) 2.19 (1.44 to 3.31); RTI 2.18 (1.71 to 2.78)). The risks for both outcomes were significantly higher in current compared with former smokers (CVE 1.51 (1.04 to 2.19), RTI 1.29 (1.04 to 1.61)). For each additional year of smoking cessation, the risk of first CVE and RTI hospitalisation fell significantly, approximately 25% and 15% respectively in the adjusted models. CONCLUSIONS: Patients with RA who smoke have an increased risk of hospitalisation with CVE or RTI compared with never and former smokers. The risk decreases for each additional year of smoking cessation. Patients with RA who smoke should be advised to stop smoking.
28420093 Potential Role of Free Fatty Acids in the Pathogenesis of Periodontitis and Primary Sjögr 2017 Apr 14 Clinical studies have shown that metabolic disorders such as type 2 diabetes and dyslipidemia are associated with increased risk of oral-related diseases, such as periodontitis and Sjögren's syndrome. Although changes in the immune system are critical in both of these metabolic disorders and oral-related diseases, the mechanism underlying the interaction between these diseases remains largely unknown. Obesity and type 2 diabetes are known to be associated with higher concentrations of free fatty acids in blood. Among free fatty acids, saturated fatty acids such as palmitic acid have been demonstrated to induce inflammatory responses mainly via the innate immune systems, and to be involved in the pathogenesis of type 2 diabetes in tissues such as adipose tissue, liver, pancreas, and skeletal muscle. Here, we highlight recent advances in evidence for the potential involvement of palmitic acid in the pathogenesis of periodontitis and Sjögren's syndrome, and discuss the possibility that improvement of the lipid profile could be a new strategy for the treatment of these diseases.
28560466 Real-life effectiveness of spa therapy in rheumatic and musculoskeletal diseases: a retros 2017 Nov The objective of this study is to determine the use and efficacy of spa therapy in patients with a wide spectrum of rheumatic and musculoskeletal diseases under real-life clinical practice circumstances. In this retrospective observational study at the Medical Ecology and Hydroclimatology Department of Istanbul Faculty of Medicine, the records of all adult patients with rheumatic and musculoskeletal diseases who were prescribed a spa therapy in various health resorts in Turkey between 2002 and 2012 were analyzed. Patients sojourned to and stayed at a health resort and followed a usual 2-week course of spa therapy. The patients were examined within a week before and after the spa therapy at the department by the physicians and outcome measures were pain intensity (visual analog scale, VAS), patient's general evaluation (VAS), physician's general evaluation (VAS), Health Assessment Questionnaire (HAQ), Lequesne's Functional Index (LFI), Western Ontario and McMaster Universities Index (WOMAC), Waddell Index (WI), Neck Pain and Disability Scale (NPDS), Shoulder Disability Questionnaire (SDQ), Fibromyalgia Impact Questionnaire (FIQ), and Beck's Depression Inventory (BDI). In total, 819 patients were included in the analysis. The diagnoses were 536 osteoarthritis; 115 fibromyalgia; 50 lumbar disc herniation; 34 cervical disc herniation; 23 nonspecific low back pain; 22 ankylosing spondylitis; 16 rheumatoid arthritis; 9 rotator cuff tendinitis; and 14 other conditions/diseases including scoliosis, stenosing flexor tenosynovitis, congenital hip dislocation in adult, Behçet's disease, de Quervain tendinopathy, psoriatic arthritis, osteoporosis, fracture rehabilitation, and diffuse idiopathic skeletal hyperostosis. Statistically significant decrease in pain scores was found in all patients except hip osteoarthritis (p = 0.063) and rheumatoid arthritis (p = 0.134) subgroups; and statistically significant improvement in function in all patients except hip osteoarthritis (p = 0.068), rheumatoid arthritis (p = 0.111), and rotator cuff tendinitis (p = 0.078) subgroups. In daily clinical practice, spa therapy is prescribed and practiced mainly for osteoarthritis, then fibromyalgia, lumbar/cervical disc herniation, and nonspecific low back pain; and less for ankylosing spondylitis, rheumatoid arthritis, and rotator cuff tendinitis. The study results suggest that real-life spa therapy may be effective in a variety of rheumatic and musculoskeletal diseases by improving pain and function.
30936951 Risk factors associated with periprosthetic joint infection after total elbow arthroplasty 2019 Apr BACKGROUND: For patients undergoing total elbow arthroplasty (TEA), the present study aimed to investigate: (i) what risk factors are associated with periprosthetic elbow infection; (ii) what is the incidence of infection after TEA; and (iii) what is the acuity with which these infections present? METHODS: The Statewide Planning and Research Cooperative System database was used to identify all patients who underwent TEA between 2003 and 2012 in New York State. Admissions for prosthetic joint infection (PJI) were identified using ICD-9 (International Classification of Diseases, Ninth Revision, Clinical Modification) diagnosis code 996.66. Multivariate analysis was used to determine risk factors that were independently prognostic for PJI. RESULTS: Significant risk factors for PJI included hypothyroidism [odds ratio (OR) = 2.04; p = 0.045], tobacco use disorder (OR = 3.39; p = 0.003) and rheumatoid arthritis (OR = 3.31; p < 0.001). Among the 1452 patients in the study period who underwent TEA, 3.7% (n = 54) were admitted postoperatively for PJI. There were 30 (56%) early infections, 17 (31%) delayed infections and seven (13%) late infections. CONCLUSIONS: Pre-operative optimization of thyroid function, smoking cessation and management of rheumatoid disease may be considered in surgical candidates for TEA. The results of the present study add prognostic data to the literature that may be helpful with patient selection and risk profile analysis. LEVEL OF EVIDENCE: Level III: prognostic study.
28620392 Interleukin-25 Produced by Synoviocytes Has Anti-inflammatory Effects by Acting As a Recep 2017 The production and function of cytokines are highly regulated. One mechanism is the balance between pro- and anti-inflammatory cytokines. As interleukin (IL)-17A and IL-25 share the IL-17RA receptor chain, we hypothesize that IL-25 acts as an IL-17A receptor antagonist and limits its pro-inflammatory effects. The production and expression kinetics of IL-25 and its receptor chains IL-17RA and RB were analyzed in rheumatoid synoviocytes alone or in coculture with peripheral blood mononuclear cells (PBMCs). The effects of autocrine or exogenous IL-25 on synoviocytes were investigated in the presence or not of an anti-IL-25 antibody. To study the regulatory effects of IL-25, synoviocytes and/or PBMCs were exposed to IL-25 before being treated with IL-17A and tumor necrosis factor alpha (TNF-α) alone or combined. IL-25, IL-6, and bioactive IL-17A were quantified in rheumatoid arthritis (RA) patient plasma. Synoviocytes expressed and secreted IL-25, and expressed the two chains of its receptor IL-17RA and IL-17RB. IL-17RB expression was increased by TNF-α. IL-25 production occurred at a delayed time point (5 days) after stimulation with IL-17A and TNF-α. Synoviocytes pretreated with IL-25 were less responsive to IL-17A and TNF-α. PBMCs exposed to IL-25 showed a decreased production of pro-inflammatory mediators, including IL-17A with a 57% decrease; p = 0.002. IL-25 levels were elevated in the plasma of RA patients compared to healthy subjects (p = 0.03). However, these levels are not high enough to inhibit the function of circulating IL-17A. In conclusion, it was shown for the first time that synoviocytes produce IL-25, specifically at late time points and that IL-25 acts as a regulator of IL-17A-driven inflammation, as indicated by in vitro results and in vivo, in a long-term RA patient follow-up. These results may be important when considering IL-17A inhibition.
28901438 Lysyl oxidase is involved in synovial hyperplasia and angiogenesis in rats with collagen†2017 Nov Lysyl oxidase (LOX) serves an important role in remodeling the extracellular matrix and angiogenesis in various types of cancer; however, whether LOX is involved in the pathogenesis of rheumatoid arthritis remains unknown. In order to investigate this in the present study, β‑aminopropionitrile, an inhibitor of LOX, was injected intraperitoneally into rats with type II collagen‑induced arthritis (CIA). Subsequently, synovial hyperplasia was examined by hematoxyl in and eosin staining, and the microvascular density (MVD) and expression levels of LOX, matrix metalloproteinase (MMP)‑2 and MMP‑9 in the synovial membrane and fluid were determined by immunohistochemistry and ELISA, respectively. The enzyme activity of LOX was evaluated by the Amplex Red Hydrogen Peroxide method. The results demonstrated an increased amount of rough synovial membranes, higher MVD in these membranes and more synovial cell layers in CIA rats compared with in the control rats. In addition, higher enzymatic activity of LOX and higher expression levels of MMP‑2 and MMP‑9 were revealed in CIA rats compared with in the control rats. Notably, β‑aminopropionitrile inhibited paw swelling and the decreased the arthritis index, the MVD in the synovial membranes and the expression levels of MMP‑2 and MMP‑9. Furthermore, the expression level of LOX in the synovial membranes was positively associated with the MVD and the expression levels of MMP‑2 and MMP‑9, suggesting that LOX promotes synovial hyperplasia and angiogenesis and that LOX may be a potential therapeutic target for rheumatoid arthritis.
28239353 Transient Receptor Potential Ankyrin 1 Channel Expression on Peripheral Blood Leukocytes f 2017 Patients with rheumatoid arthritis (RA) suffer from pain and joint disability. The transient receptor potential ankyrin 1 (TRPA1) channel expressed on sensory neurones and non-neuronal cells mediates pain transduction and inflammation and it has been implicated in RA. However, there is little information on the contribution of TRPA1 for human disease. Here, we investigated the expression of TRPA1 on peripheral blood leukocytes and the circulating levels of its endogenous activators 4-hydroxynonenal (4-HNE) and hydrogen peroxide (H(2)O(2)) in RA patients treated or not with the anti-rheumatic leflunomide (LFN) or the anti-TNFα adalimumab (ADA). We also assessed whether TRPA1 expression correlates with joint pain and disability, in addition to the immune changes in RA. TRPA1 expression on peripheral blood leukocytes correlated with pain severity and disability. TRPA1 levels on these cells were associated with the numbers of polymorphonuclear and the activation of CD14(+) cells. No correlations were found between the lymphocyte population and TRPA1 expression, pain or disability. Patients recently diagnosed with RA expressed increased levels of TRPA1 on their leukocytes whilst treatment with either LFN or ADA down-regulated this receptor probably by reducing the numbers of polymorphonuclears and the activation of CD14(+) cells. We suggest that the activation levels of CD14(+) cells, the numbers of PMNs in the peripheral blood and the expression of TRPA1 on peripheral blood leukocytes correlate with RA progression, affecting joint pain sensitivity and loss of function.
28955491 Effect of celastrol on bone structure and mechanics in arthritic rats. 2017 OBJECTIVE: Rheumatoid arthritis (RA) is characterised by chronic inflammation leading to articular bone and cartilage damage. Despite recent progress in RA management, adverse effects, lack of efficacy and economic barriers to treatment access still limit therapeutic success. Therefore, safer and less expensive treatments that control inflammation and bone resorption are needed. We have previously shown that celastrol is a candidate for RA treatment. We have observed that it inhibits both interleukin (IL)-1β and tumor necrosis factor (TNF) in vitro, and that it has anti-inflammatory properties and ability to decrease synovial CD68+ macrophages in vivo. Herein our goal was to evaluate the effect of celastrol in local and systemic bone loss. METHODS: Celastrol was administrated intraperitoneally at a dose of 1 µg/g/day to female Wistar adjuvant-induced arthritic rats. Rats were sacrificed after 22 days of disease progression, and blood, femurs, tibiae and paw samples were collected for bone remodelling markers quantification, 3-point bending test, micro-CT analysis, nanoindentation and Fourier transform infrared spectroscopy measurements, and immunohistochemical evaluation. RESULTS: We have observed that celastrol preserved articular structures and decreased the number of osteoclasts and osteoblasts present in arthritic joints. Moreover, celastrol reduced tartrate-resistant acid phosphatase 5b, procollagen type 1 amino-terminal propeptide and C terminal crosslinked telopeptide of type II collagen serum levels. Importantly, celastrol prevented bone loss and bone microarchitecture degradation. Celastrol also preserved bone nanoproperties and mineral content. Additionally, animals treated with celastrol had less fragile bones, as depicted by an increase in maximum load and yield displacement. CONCLUSIONS: These results suggest that celastrol reduces both bone resorption and cartilage degradation, and preserves bone structural properties.
29228993 Programmed cell death 5 transgenic mice attenuates adjuvant induced arthritis by 2 modifyi 2017 Dec 11 BACKGROUND: Programmed cell death 5 (PDCD5) is an apoptosis-related gene cloned from TF-1 cells whose primary biological functions are to promote apoptosis and immune regulation. The effects and mechanisms exerted by key mediators of arthritic inflammation remain unclear in PDCD5 transgenic (PDCD5 tg) mice. RESULTS: In the current study, PDCD5 tg mice inhibited the progression of adjuvant-induced arthritis, specifically decreasing clinical signs and histological damage, compared with arthritis control mice. Additionally, the ratio of CD4(+)IFN-γ(+) cells (Th1) and CD4(+)IL-17A(+) cells (Th17), as well as the mRNA expression of the pro-inflammatory mediators IFN-γ, IL-6, IL-17A and TNF-α, were decreased in PDCD5 tg mice, while CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells and the anti-inflammatory mediators IL-4 and IL-10 were increased. Furthermore, PDCD5 tg mice demonstrated reduced serum levels of IFN-γ, IL-6, IL-17A and TNF-α and increased levels of IL-4. CONCLUSIONS: Based on our data, PDCD5 exerts anti-inflammatory effects by modifying the T lymphocytes balance, inhibiting the production of pro-inflammatory mediators and promoting the secretion of anti-inflammatory cytokines, validating PDCD5 protein as a possible treatment for RA.
28465323 13-Series resolvins mediate the leukocyte-platelet actions of atorvastatin and pravastatin 2017 Aug Rheumatoid arthritis is an inflammatory condition characterized by overzealous inflammation that leads to joint damage and is associated with an increased incidence of cardiovascular disease. Statins are frontline therapeutics for patients with cardiovascular disease and exert beneficial actions in rheumatoid arthritis. The mechanism that mediates the beneficial actions of statins in rheumatoid arthritis remains of interest. In the present study, we found that the administration of 2 clinically relevant statins-atorvastatin (0.2 mg/kg) or pravastatin (0.2 mg/kg)-to mice during inflammatory arthritis up-regulated systemic and tissue amounts of a novel family of proresolving mediators, termed 13-series resolvins (RvTs), and significantly reduced joint disease. Of note, administration of simvastatin (0.2 mg/kg) did not significantly up-regulate RvTs or reduce joint inflammation. We also found that atorvastatin and pravastatin each reduced systemic leukocyte activation, including platelet-monocyte aggregates (∼25-60%). These statins decreased neutrophil trafficking to the joint as well as joint monocyte and macrophage numbers. Atorvastatin and pravastatin produced significant reductions (∼30-50%) in expression of CD11b and major histocompatibility complex class II on both monocytes and monocyte-derived macrophages in joints. Administration of an inhibitor to cyclooxygenase-2, the initiating enzyme in the RvT pathway, reversed the protective actions of these statins on both joint and systemic inflammation. Together, these findings provide evidence for the role of RvTs in mediating the protective actions of atorvastatin and pravastatin in reducing local and vascular inflammation, and suggest that RvTs may be useful in measuring the anti-inflammatory actions of statins.-Walker, M. E., Souza, P. R., Colas, R. A., Dalli, J. 13-Series resolvins mediate the leukocyte-platelet actions of atorvastatin and pravastatin in inflammatory arthritis.
28723775 The neutrophil-to-lymphocyte ratio could be a good diagnostic marker and predictor of rela 2017 Jul The neutrophil-to-lymphocyte ratio (NLR) is the proportion of absolute neutrophil count to lymphocytes on routine complete blood count (CBC) tests, and has been studied as a simple marker of the systemic inflammatory response. This study was performed to investigate whether the NLR could be used as a tool to diagnose and predict prognosis in cases of adult-onset Still's disease (AOSD).We retrospectively reviewed 164 patients with suspected AOSD. Among 164 patients with suspected AOSD, 37 patients received another diagnosis (such as viral infection) and were compared with the 127 patients who received a diagnosis of AOSD. Laboratory tests including CBCs, ferritin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and the NLR were evaluated.AOSD patients showed higher neutrophil counts, lower lymphocyte counts, higher NLRs, and higher levels of ferritin, ESR, and CRP than non-AOSD patients (all P < .001). In receiver operating characteristic (ROC) curve analysis of the NLR for diagnosis of AOSD, the area under the curve (AUC) was highest at 0.967 (95% CI = 0.940-0.993) with a cutoff value of 3.08. The cutoff value showed the greatest sensitivity (91.7%), specificity (68.4%), and AUC value (0.967) as a diagnostic tool for AOSD. The NLR and treatment appeared to be significant prognostic factors for relapse, but only age showed a significant relationship with death. Furthermore, the NLR was significantly higher in patients with macrophage activation syndrome than in hemophagocytic lymphohistiocytosis (HLH) patients (P = .007). In ROC analysis, the NLR with a cutoff value of 5.86 showed a sensitivity of 89.4%, specificity of 87.8%, and AUC of 0.794.The NLR can be used as a diagnostic tool and predictor of relapse in AOSD, and for differential diagnosis of HLH.
29071588 A Retrospective Medical Record Review of Utilization Patterns and Medical Resource Use Ass 2017 Dec INTRODUCTION: Repository corticotropin injection (RCI) has anti-inflammatory and immune-modulatory effects and is approved for multiple indications, including several rheumatologic conditions. The aims of this nationally representative, retrospective, observational study were to describe patient characteristics, RCI treatment patterns, and barriers to RCI use in patients with rheumatologic disease, and to compare medical resource use (MRU) before and after RCI therapy. METHODS: A random sample of US physicians was recruited to abstract the medical records of deidentified patients with a diagnosis of rheumatoid arthritis (RA), psoriatic arthritis (PsA), dermatomyositis/polymyositis (DM/PM), or systemic lupus erythematosus (SLE) who had been treated with RCI in the previous 24 months. Patient characteristics and patterns of RCI use were identified. Mean MRU in the 3 months before and after RCI therapy was compared using paired-samples t tests. RESULTS: A total of 449 physicians abstracted the medical records of 217 RA, 190 PsA, 254 DM/PM, and 95 SLE patients. In all groups combined, patients had received a mean of 3.3 treatment medications before initiating RCI. Most patients (75%-94%) were receiving RCI for the first time, indicating that repeated courses of RCI were uncommon. RCI was used as bridge therapy in 18% of patients. Approximately 24% of patients encountered an obstacle in accessing RCI, primarily insurance-related. After RCI therapy, the number of hospitalizations and hospital days were significantly reduced for all cohorts (all P < 0.05), and the number of outpatient visits was significantly lower for all cohorts (P < 0.05) except the SLE cohort (P = 0.3230). Study limitations include potentially incomplete data in the medical records and a relatively short duration for capturing MRU changes. CONCLUSIONS: RCI was used primarily as late-line therapy in patients with rheumatologic diseases. Medical resource use was significantly lower in the 3 months after therapy compared with 3 months prior. This finding suggests that RCI may improve disease control and warrants further evaluation. FUNDING: Mallinckrodt Pharmaceuticals.
28276715 Inflammation in Sjögren's syndrome: Cause or consequence? 2017 May Sjögren's syndrome (SS) is an autoimmune disease most commonly characterized by ocular and oral dryness. Despite the high prevalence of SS, generation and perpetuation of this disease is still unclear in many aspects. Inflammation, nonetheless, seems to play a central role in this pathology especially in the form of Th-1, Th-2 and Th-17 cytokines release within different aspects, concentrations and connections involved in the maintenance of the syndrome. Moreover, the chronically created pro-inflammatory environment appears to promote glandular atrophy and irreparable architectural modifications. The establishment of germinal centers (GC) in SS are considered the main reason for the 16-times increased probability of lymphoproliferative disease development in these patients. SS is also interconnected with numerous others auto-inflammatory and autoimmune diseases, many of them representing the first clear sign of a dysregulated immune system. Despite the recent advances, treatment options are still insufficient. This overview aims to better elucidate this local and systemic disease, which can be of vital use not only for SS but also to other rheumatic pathological conditions.